The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis
Fransquet PD, Wrigglesworth J, Woods RL, Ernst ME, Ryan J.. Clinical epigenetics, 2019-04-11
Topic: Genetics and APOE
Background Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk. Methods A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality. Results Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality. Conclusion Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.
Key findings
- Results Twenty-three relevant articles were identified, including a total of 41,607 participants.
- Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality.
- Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered.
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Study details
- Study designsystematic review
- Participants41,607
- Evidence strengthHigh
How this study scored 81/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 47 of the 58 points we could judge it on, which is 81 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical epigenetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 4 / 4 | 41,607 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30975202) |
| Free to read | 2 / 2 | Free to read |
| Points | 47 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 47 of the 58 points we could judge it on is 81 out of 100. |
| Total | 81 / 100 | — |
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APA 7th
Fransquet, P. D., Wrigglesworth, J., Woods, R. L., Ernst, M. E., & Ryan, J. (2019). The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis. Clinical epigenetics. https://doi.org/10.1186/s13148-019-0656-7
Vancouver
Fransquet PD, Wrigglesworth J, Woods RL, Ernst ME, Ryan J. The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis. Clinical epigenetics. 2019. doi:10.1186/s13148-019-0656-7. PMID: 30975202.
BibTeX
@article{fransquet2019-30975202,
author = {Fransquet, P. D. and Wrigglesworth, J. and Woods, R. L. and Ernst, M. E. and Ryan, J.},
title = {{The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis}},
journal = {Clinical epigenetics},
year = {2019},
doi = {10.1186/s13148-019-0656-7},
pmid = {30975202},
url = {https://doi.org/10.1186/s13148-019-0656-7}
}